Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0026331
Title: Effects of Sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with refractory sarcomas (NCI protocol 6948)
Authors: Raut C.P.
Boucher Y.
Duda D.G.
Morgan J.A.
Quek R. 
Ancukiewicz M.
Lahdenranta J.
Eder J.P.
Demetri G.D.
Jain R.K.
Keywords: biological marker
placental growth factor
sorafenib
stromal cell derived factor 1alpha
vasculotropin
vasculotropin receptor 2
angiogenic protein
antineoplastic agent
benzenesulfonic acid derivative
protein kinase inhibitor
pyridine derivative
sorafenib
tumor marker
vasculotropin
adult
advanced cancer
aged
alopecia
anorexia
article
blood vessel permeability
cancer patient
clinical article
continuous infusion
controlled study
dehydration
desquamation
diarrhea
disease course
drug efficacy
drug eruption
drug fever
erythema multiforme
erythrocyte count
fatigue
female
hand foot syndrome
hemoglobin blood level
human
human cell
human tissue
hypertension
leg pain
male
mouth pain
mucosa inflammation
myalgia
phase 2 clinical trial
protein blood level
protein synthesis inhibition
pruritus
side effect
skin toxicity
soft tissue sarcoma
stomatitis
thrombocyte
tissue pressure
tumor biopsy
tumor volume
blood
capillary permeability
clinical trial
drug effect
extracellular fluid
middle aged
pressure
salvage therapy
sarcoma
Adult
Aged
Aged, 80 and over
Angiogenic Proteins
Antineoplastic Agents
Benzenesulfonates
Capillary Permeability
Extracellular Fluid
Female
Humans
Male
Middle Aged
Pressure
Protein Kinase Inhibitors
Pyridines
Salvage Therapy
Sarcoma
Tumor Markers, Biological
Vascular Endothelial Growth Factors
Issue Date: 2012
Citation: Raut C.P., Boucher Y., Duda D.G., Morgan J.A., Quek R., Ancukiewicz M., Lahdenranta J., Eder J.P., Demetri G.D., Jain R.K. (2012). Effects of Sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with refractory sarcomas (NCI protocol 6948). PLoS ONE 7 (2) : e26331. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0026331
Rights: Attribution 4.0 International
Abstract: Purpose: Sorafenib is a multi-targeted tyrosine kinase inhibitor with therapeutic efficacy in several malignancies. Sorafenib may exert its anti-neoplastic effect in part by altering vascular permeability and reducing intra-tumoral interstitial hypertension. As correlative science with a phase II study in patients with advanced soft-tissue sarcomas (STS), we evaluated the impact of this agent on intra-tumor interstitial fluid pressure (IFP), serum circulating biomarkers, and vascular density. Patients and Methods: Patients with advanced STS with measurable disease and at least one superficial lesion amenable to biopsy received sorafenib 400 mg twice daily. Intratumoral IFP and plasma and circulating cell biomarkers were measured before and after 1-2 months of sorafenib administration. Results were analyzed in the context of the primary clinical endpoint of time-to-progression (TTP). Results: In 15 patients accrued, the median TTP was 45 days (range 14-228). Intra-tumoral IFP measurements obtained in 6 patients at baseline showed a direct correlation with tumor size. Two patients with stable disease at two months had post-sorafenib IFP evaluations and demonstrated a decline in IFP and vascular density. Sorafenib significantly increased plasma VEGF, PlGF, and SDF1? and decreased sVEGFR-2 levels. Increased plasma SDF1? and decreased sVEGFR-2 levels on day 28 correlated with disease progression. Conclusions: Pretreatment intra-tumoral IFP correlated with tumor size and decreased in two evaluable patients with SD on sorafenib. Sorafenib also induced changes in circulating biomarkers consistent with expected VEGF pathway blockade, despite the lack of more striking clinical activity in this small series. © 2012 Raut et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/162003
ISSN: 19326203
DOI: 10.1371/journal.pone.0026331
Rights: Attribution 4.0 International
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